Baptista Trino, Sandia Ignacio, Lacruz Anny, Rangel Nairy, de Mendoza Soaira, Beaulieu Serge, Contreras Quilianio, Galeazzi Tatiana, Vargas Doritza
Department of Physiology, Los Andes University Medical School, San Cristóbal, Venezuela.
Int Clin Psychopharmacol. 2007 Mar;22(2):69-76. doi: 10.1097/YIC.0b013e32801182e6.
In this study, the Authors assessed some insulin counter-regulatory factors, fibrinogen and C-reactive protein after olanzapine administration, and the effect of metformin on these variables, 37 patients with chronic schizophrenia were given olanzapine (10 mg/day for 14 weeks). Nineteen patients received metformin (850-2550 mg/day) and 18 received placebo in a randomized, double-blind protocol. The following variables were quantified before and after olanzapine: cortisol, leptin, tumor necrosis factor-alpha, glucagon, growth hormone, fibrinogen and C-reactive protein. Results were correlated with the changes in body weight and the insulin resistance index. We have reported elsewhere that metformin did not prevent olanzapine-induced weight gain, and the insulin resistance index significantly decreased after metformin and placebo; Baptista T, et al. Can J Psychiatry 2006; 51: 192-196. Cortisol, tumor necrosis factor-alpha and fibrinogen levels significantly decreased in both groups. Glucagon significantly increased after metformin (P=0.03). Leptin tended to increase after placebo (P=0.1) and displayed a small nonsignificant reduction after metformin. The C-reactive protein did not change significantly in any group. Contrarily to most published studies, olanzapine was associated with decreased insulin resistance. Decrements in cortisol, fibrinogen and tumor necrosis factor-alpha levels point to an improvement in the metabolic profile. The trend for leptin to increase after placebo, but not after metformin in spite of similar weight gain suggests a beneficial effect of this antidiabetic agent.
在本研究中，作者评估了奥氮平给药后一些胰岛素对抗调节因子、纤维蛋白原和C反应蛋白，以及二甲双胍对这些变量的影响。37例慢性精神分裂症患者接受奥氮平治疗（10mg/天，共14周）。19例患者接受二甲双胍治疗（850 - 2550mg/天），18例患者接受安慰剂，采用随机双盲方案。在奥氮平治疗前后对以下变量进行量化：皮质醇、瘦素、肿瘤坏死因子-α、胰高血糖素、生长激素、纤维蛋白原和C反应蛋白。结果与体重变化和胰岛素抵抗指数相关。我们在其他地方报道过，二甲双胍不能预防奥氮平引起的体重增加，二甲双胍和安慰剂治疗后胰岛素抵抗指数均显著下降；Baptista T等人，《加拿大精神病学杂志》2006年；51: 192 - 196。两组患者的皮质醇、肿瘤坏死因子-α和纤维蛋白原水平均显著下降。二甲双胍治疗后胰高血糖素显著升高（P = 0.03）。安慰剂治疗后瘦素呈上升趋势（P = 0.1），二甲双胍治疗后瘦素略有下降但无显著差异。任何一组中C反应蛋白均无显著变化。与大多数已发表的研究相反，奥氮平与胰岛素抵抗降低有关。皮质醇、纤维蛋白原和肿瘤坏死因子-α水平的下降表明代谢状况有所改善。尽管体重增加相似，但安慰剂治疗后瘦素有上升趋势，而二甲双胍治疗后则无，这表明这种抗糖尿病药物具有有益作用。
